Cytochrome p450 1B1 polymorphisms and risk of renal cell carcinoma in men

Inik Chang, Shinichiro Fukuhara, Darryn K. Wong, Ankurpreet Gill, Yozo Mitsui, Shahana Majid, Sharanjot Saini, Soichiro Yamamura, Takeshi Chiyomaru, Hiroshi Hirata, Koji Ueno, Sumit Arora, Varahram Shahryari, Guoren Deng, Z. Laura Tabatabai, Kirsten L. Greene, Dong Min Shin, Hideki Enokida, Hiroaki Shiina, Norio NonomuraRajvir Dahiya, Yuichiro Tanaka

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Abstract

The cytochrome P450 1B1 (CYP1B1) enzyme activates xenobiotics to reactive forms as well as convert estra-diol to 4-hydroxy-estradiol that has been shown to play a role in the carcinogenesis process of the kidney in male but not female animals. Prior reports show polymorphic variants of CYP1B1 to alter catalytic activity, and thus, we hypothesize that polymorphisms of the CYP1B1 gene are involved in the malignant transformation of the renal cell in men. The genetic distributions of five CYP1B1 polymorphisms were analyzed by polymerase chain reaction–restriction fragment length polymorphism in 480 normal healthy subjects and 403 sporadic renal cell carcinoma cases. All subjects were Caucasian men. The sites evaluated were codons 48 (C→G, Arg→Gly, rs10012), 119 (G→T, Ala→Ser, rs1056827), 432 (C→G, Leu→Val, rs1056836), 449 (C→T, Asp, rs1056837), and 453 (A→G, Asn→Ser, rs1800440). A trend was demonstrated for the 432 Val/Val (χ2, P=0.06) and 449 T/T (χ2, P=0.1) genotypes to play a protective role against renal cancer. Odds ratio (95% confidence interval) for Val/Val compared to Leu/ Leu at codon 432 was 0.65 (0.44–0.95) and T/T compared to C/C at codon 449 was 0.67 (0.45–0.99). Codons 432 and 449 were observed to be linked (D=0.24), and haplotype involving 432 Val and 449 T was significantly reduced in cancer cases (P=0.04). No association was found, however, when analyzing polymorphic sites with clinical stage of cancer. These results demonstrate polymorphisms of CYP1B1 to be associated with renal carcinogenesis and are of importance in understanding their role in the pathogenesis of renal cell carcinoma.

Original languageEnglish
Pages (from-to)10223-10230
Number of pages8
JournalTumor Biology
Volume35
Issue number10
DOIs
Publication statusPublished - 2014

All Science Journal Classification (ASJC) codes

  • Cancer Research

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    Chang, I., Fukuhara, S., Wong, D. K., Gill, A., Mitsui, Y., Majid, S., Saini, S., Yamamura, S., Chiyomaru, T., Hirata, H., Ueno, K., Arora, S., Shahryari, V., Deng, G., Laura Tabatabai, Z., Greene, K. L., Shin, D. M., Enokida, H., Shiina, H., ... Tanaka, Y. (2014). Cytochrome p450 1B1 polymorphisms and risk of renal cell carcinoma in men. Tumor Biology, 35(10), 10223-10230. https://doi.org/10.1007/s13277-014-2292-3